Journal of the Pediatric Infectious Diseases Society, 2014
Background. Rhinovirus is the most common cause of viral respiratory tract infections in children... more Background. Rhinovirus is the most common cause of viral respiratory tract infections in children. Virologic predictors of lower respiratory tract infection (LRTI), such as viral load and the presence of another respiratory virus (coinfection), are not well characterized in pediatric outpatients. Methods. Mid-nasal turbinate samples were collected from children presenting for care to the Seattle Children's Hospital emergency department (ED) or urgent care with a symptomatic respiratory infection between December 2011 and May 2013. A subset of samples was tested for rhinovirus viral load by real-time polymerase chain reaction. Clinical data were collected by chart reviews. Multivariate logistic regression was used to evaluate the relationship between viral load and coinfection and the risk for LRTI. Results. Rhinovirus was the most frequent respiratory virus detected in children younger than 3 years. Of 445 patients with rhinovirus infection, 262 (58.9%) had LRTIs, 231 (51.9%) required hospital admission and 52 (22.5%) were hospitalized for 3 days or longer. Children with no comorbidities accounted for 142 (54%) of 262 rhinovirus LRTIs. Higher viral load was significantly associated with LRTI among illness episodes with rhinovirus alone (OR, 2.11; 95% confidence interval [CI], 1.24-3.58). Coinfection increased the risk of LRTI (OR, 1.83; 95% CI, 1.01-3.32). Conclusions. Rhinovirus was the most common pathogen detected among symptomatic young children in a pediatric ED who had respiratory viral testing performed, with the majority requiring hospitalization. Higher rhinovirus viral load and coinfection increased disease severity. Virologic data may assist clinical decision making for children with rhinovirus infections in the pediatric ED.
We managed recently a boy with acute parvovirus infection. A 14-yearold boy with hereditary spher... more We managed recently a boy with acute parvovirus infection. A 14-yearold boy with hereditary spherocytosis was brought to the hospital in shock. He had a 1-week history of fever, watery diarrhea and vomiting. On arrival, he was jaundiced and lethargic. Temperature was 38.1°C, heart rate 160/min, respiratory rate 28/min, blood pressure 90/40 mm Hg and O 2 saturation 94%. Splenomegaly unchanged from previous was present. Rash was absent, and he was mildly dehydrated.
N-(2-Hydroxypropyl) methacrylamide copolymer-5-fluorouracil (PHPMA-FU) conjugates were synthesize... more N-(2-Hydroxypropyl) methacrylamide copolymer-5-fluorouracil (PHPMA-FU) conjugates were synthesized by a novel and simplified synthetic route, and characterized by UV, FTIR and HPLC analyses. The conjugated content of 5-fluorouracil (5-FU) was 3.41±0.07wt%. The stabilities of PHPMA-FU conjugates under different conditions were studied. The results showed that HPMA copolymer was a potential carrier for tumor-targeting delivery of 5-FU.
We evaluated the Meridian IC-STAT direct fecal and broth culture antigen detection methods with s... more We evaluated the Meridian IC-STAT direct fecal and broth culture antigen detection methods with samples from children infected with Escherichia coli O157:H7 and correlated the antigen detection results with the culture results. Stools of 16 children who had recently had stool cultures positive for this pathogen (population A) and 102 children with diarrhea of unknown cause (population B) were tested with the IC-STAT device (direct testing). Fecal broth cultures were also tested with this device (broth testing). The results were correlated to a standard of the combined yield from direct culture of stools on sorbitol-MacConkey (SMAC) agar and culture of broth on SMAC agar. Eleven (69%) of the population A stool specimens yielded E. coli O157:H7 when plated directly on SMAC agar. Two more specimens yielded this pathogen when the broth culture was similarly plated. Of these 13 stool specimens, 8 and 13 were positive by direct and broth testing (respective sensitivities, 62 and 100%). Co...
The objective of this study is to describe the epidemiology of intestinal carriage with extended-... more The objective of this study is to describe the epidemiology of intestinal carriage with extended-spectrum-cephalosporin-resistant Enterobacteriaceae in children with index infections with these organisms. Patients with resistant Escherichia coli or Klebsiella bacteria isolated from the urine or a normally sterile site between January 2006 and December 2010 were included in this study. Available infection and stool isolates underwent phenotypic and molecular characterization. Clinical data relevant to the infections were collected and analyzed. Overall, 105 patients were identified with 106 extended-spectrum-cephalosporin-resistant E. coli (n = 92) or Klebsiella (n = 14) strains isolated from urine or a sterile site. Among the 27 patients who also had stool screening for resistant Enterobacteriaceae, 17 (63%) had intestinal carriage lasting a median of 199 days (range, 62 to 1,576). There were no significant differences in demographic, clinical, and microbiological variables between ...
To conduct a prospective cohort study to determine the frequency and characteristics of Shiga tox... more To conduct a prospective cohort study to determine the frequency and characteristics of Shiga toxin (Stx)-producing Escherichia coli (STEC) infections in children with diarrhea attending an emergency department and a private clinic in Seattle, Washington.
Annals of clinical microbiology and antimicrobials, Jan 15, 2004
Resistance to beta-lactam antibiotics in enteric Gram-negative bacilli may be difficult to detect... more Resistance to beta-lactam antibiotics in enteric Gram-negative bacilli may be difficult to detect using standard methods of either Kirby-Bauer disc diffusion (KBDD) or broth dilution for minimal inhibitory concentration (MIC). This difficulty is due to genetic differences in resistance determinants, differences in levels of gene expression, and variation in spectra of enzymatic activity against the substrate beta-lactams used for susceptibility testing. We have examined 95 clinical isolates reportedly susceptible to ceftazidime and ceftriaxone, as originally determined by either KBDD or MIC methods. The organisms studied here were isolated in 2002 from two pediatric hospital centers (Seattle, USA and Shanghai, China). They belong to the inducible beta-lactamase producing Gram-negative bacilli, such as Enterobacter spp., Citrobacter spp., Serratia spp., Morganella spp., Providencia spp., and Proteus vulgaris. A Kirby-Bauer disc approximation (KBDA) method identified inducible phenoty...
Background. A recent increase in Bordetella pertussis without the pertactin protein, an acellular... more Background. A recent increase in Bordetella pertussis without the pertactin protein, an acellular vaccine immunogen, has been reported in the United States. Determining whether pertactin-deficient (PRN -) B. pertussis is evading vaccine-induced immunity or altering the severity of illness is needed.
European Journal of Pharmaceutics and Biopharmaceutics, 2008
5-Fluorouracil (5-FU) is an antimetabolite with a broad-spectrum activity against solid tumors. H... more 5-Fluorouracil (5-FU) is an antimetabolite with a broad-spectrum activity against solid tumors. However, its very short half-life in plasma circulation greatly limited the in vivo antitumor efficacy and clinical application. The current work aimed to solve this problem as well as to increase 5-FU biodistribution to tumor by covalently conjugating 5-FU to a biocompatible, non-toxic and non-immunogenic drug carrier –N-(2-hydroxypropyl)
Crohn&amp... more Crohn's disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal microbial transplant (FMT) is a potential therapeutic option for individuals with CD based on the hypothesis that changing the fecal dysbiosis could promote less intestinal inflammation. Nine patients, aged 12 to 19 years, with mild-to-moderate symptoms defined by Pediatric Crohn's Disease Activity Index (PCDAI of 10-29) were enrolled into a prospective open-label study of FMT in CD (FDA IND 14942). Patients received FMT by nasogastric tube with follow-up evaluations at 2, 6, and 12 weeks. PCDAI, C-reactive protein, and fecal calprotectin were evaluated at each study visit. All reported adverse events were graded as mild except for 1 individual who reported moderate abdominal pain after FMT. All adverse events were self-limiting. Metagenomic evaluation of stool microbiome indicated evidence of FMT engraftment in 7 of 9 patients. The mean PCDAI score improved with patients having a baseline of 19.7 ± 7.2, with improvement at 2 weeks to 6.4 ± 6.6 and at 6 weeks to 8.6 ± 4.9. Based on PCDAI, 7 of 9 patients were in remission at 2 weeks and 5 of 9 patients who did not receive additional medical therapy were in remission at 6 and 12 weeks. No or modest improvement was seen in patients who did not engraft or whose microbiome was most similar to their donor. This is the first study to demonstrate that FMT for CD may be a possible therapeutic option for CD. Further prospective studies are required to fully assess the safety and efficacy of the FMT in patients with CD.
Yakugaku Zasshi-journal of The Pharmaceutical Society of Japan, 2010
This paper reports both the optimization of aconitine entrapment and its release from biodegradab... more This paper reports both the optimization of aconitine entrapment and its release from biodegradable poly(d,l-lactide-coglycolide) (PLGA) nanoparticles prepared using the O/W single-emulsion/solvent-evaporation technique. The in‰uence of several parameters, such as the initial aconitine mass, aqueous-phase pH, volume ratio of aqueous/organic phase (W/O), PLGA concentration in the organic phase, etc., on aconitine encapsulation were investigated. The optimized nanoparticles had an entrapment e‹ciency of 88.40±3.02％ with drug loading capacity of 9.42±2.93％. Crystallization growth, which played a crucial role in hindering the incorporation of aconitine into the polymer carrier, was proposed. DiŠerential scanning calorimetry and X-ray powder diŠraction demonstrated that aconitine existed in an amorphous state or as a solid solution in the polymeric matrix. The in vitro release proˆles exhibited a sustained release of aconitine from nanoparticles and a pH-dependent character in phosphate-buŠered saline with diŠerent pH values. Moreover, aconitine-loaded PLGA nanoparticles could lead to improvement in the stability of aconitine. This work demonstrated the feasibility of encapsulating aconitine into PLGA nanoparticles using the O/W single-emulsion/solvent-evaporation technique.
International journal of pharmaceutics, Jan 12, 2008
In this study, the effects of alginate modification on absorption properties of FITC-BSA loaded T... more In this study, the effects of alginate modification on absorption properties of FITC-BSA loaded TMC nanoparticles were investigated on an in vitro model of GI epithelium (Caco-2 cells). The feasibility of applying TMC nanoparticles loaded with a model vaccine urease in oral vaccination was also studied. Alginate modified TMC nanoparticles showed higher FITC-BSA permeate efficiency than non-modified TMC nanoparticles. However, alginate modification barely had any effect on TMC nanoparticles' property of decreasing TEER or enhancing drug paracellular transport. Mice s.c. immunized with urease loaded TMC nanoparticles showed highest systematic immune response (IgG levels) but the lowest mucosal response (secretory IgA levels). In the contrast, mice i.g. immunized with urease loaded TMC nanoparticles showed much higher antibody titers of both IgG and secretory IgA than those with urease solution or urease co-administrated with TMC solution. These results indicated that TMC nanoparti...
Although pertussis disease is vaccine preventable, Washington State experienced a substantial ris... more Although pertussis disease is vaccine preventable, Washington State experienced a substantial rise in pertussis incidence beginning in 2011. By June 2012, the reported cases reached 2,520 (37.5 cases per 100,000 residents), a 1,300% increase compared with the same period in 2011. We assessed the molecular epidemiology of this statewide epidemic using 240 isolates collected from case patients reported from 19 of 39 Washington counties during 2012 to 2013. The typing methods included pulsed-field gel electrophoresis (PFGE), multilocus variable number tandem repeat analysis (MLVA), multilocus sequence typing (MLST), and pertactin gene (prn) mutational analysis. Using the scheme PFGE-MLVA-MLST-prn mutations-Prn deficiency, the 240 isolates comprised 65 distinct typing profiles. Thirty-one PFGE types were found, with the most common types, CDC013 (n = 51), CDC237 (n = 44), and CDC002 (n = 42), accounting for 57% of them. Eleven MLVA types were observed, mainly comprising type 27 (n = 183...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 15, 2015
A recent increase in Bordetella pertussis without the pertactin protein, an acellular vaccine imm... more A recent increase in Bordetella pertussis without the pertactin protein, an acellular vaccine immunogen, has been reported in the United States. Determining whether pertactin-deficient (PRN(-)) B. pertussis is evading vaccine-induced immunity or altering the severity of illness is needed. We retrospectively assessed for associations between pertactin production and both clinical presentation and vaccine history. Cases with isolates collected between May 2011 and February 2013 from 8 states were included. We calculated unadjusted and adjusted odds ratios (ORs) using multivariable logistic regression analysis. Among 753 isolates, 640 (85%) were PRN(-). The age distribution differed between cases caused by PRN(-) B. pertussis and cases caused by B. pertussis producing pertactin (PRN(+)) (P = .01). The proportion reporting individual pertussis symptoms was similar between the 2 groups, except a higher proportion of PRN(+) case-patients reported apnea (P = .005). Twenty-two case-patients...
Emerging antibiotic resistance threatens human health. Gut microbes are an epidemiologically impo... more Emerging antibiotic resistance threatens human health. Gut microbes are an epidemiologically important reservoir of resistance genes (resistome), yet prior studies indicate that the true diversity of gut-associated resistomes has been underestimated. To deeply characterize the pediatric gut-associated resistome, we created metagenomic recombinant libraries in an Escherichia coli host using fecal DNA from 22 healthy infants and children (most without recent antibiotic exposure), and performed functional selections for resistance to 18 antibiotics from eight drug classes. Resistanceconferring DNA fragments were sequenced (Illumina HiSeq 2000), and reads assembled and annotated with the PARFuMS computational pipeline. Resistance to 14 of the 18 antibiotics was found in stools of infants and children. Recovered genes included chloramphenicol acetyltransferases, drug-resistant dihydrofolate reductases, rRNA methyltransferases, transcriptional regulators, multidrug efflux pumps, and every major class of beta-lactamase, aminoglycoside-modifying enzyme, and tetracycline resistance protein. Many resistance-conferring sequences were mobilizable; some had low identity to any known organism, emphasizing cryptic organisms as potentially important resistance reservoirs. We functionally confirmed three novel resistance genes, including a 16S rRNA methylase conferring aminoglycoside resistance, and two tetracyclineresistance proteins nearly identical to a bifidobacterial MFS transporter (B. longum s. longum JDM301). We provide the first report to our knowledge of resistance to folate-synthesis inhibitors conferred by a predicted Nudix hydrolase (part of the folate synthesis pathway). This functional metagenomic survey of gut-associated resistomes, the largest of its kind to date, demonstrates that fecal resistomes of healthy children are far more diverse than previously suspected, that clinically relevant resistance genes are present even without recent selective antibiotic pressure in the human host, and that cryptic gut microbes are an important resistance reservoir. The observed transferability of gut-associated resistance genes to a gram-negative (E. coli) host also suggests that the potential for gut-associated resistomes to threaten human health by mediating antibiotic resistance in pathogens warrants further investigation.
We managed recently a boy with acute parvovirus infection. A 14-yearold boy with hereditary spher... more We managed recently a boy with acute parvovirus infection. A 14-yearold boy with hereditary spherocytosis was brought to the hospital in shock. He had a 1-week history of fever, watery diarrhea and vomiting. On arrival, he was jaundiced and lethargic. Temperature was 38.1°C, heart rate 160/min, respiratory rate 28/min, blood pressure 90/40 mm Hg and O 2 saturation 94%. Splenomegaly unchanged from previous was present. Rash was absent, and he was mildly dehydrated.
Journal of the Pediatric Infectious Diseases Society, 2014
Background. Rhinovirus is the most common cause of viral respiratory tract infections in children... more Background. Rhinovirus is the most common cause of viral respiratory tract infections in children. Virologic predictors of lower respiratory tract infection (LRTI), such as viral load and the presence of another respiratory virus (coinfection), are not well characterized in pediatric outpatients. Methods. Mid-nasal turbinate samples were collected from children presenting for care to the Seattle Children's Hospital emergency department (ED) or urgent care with a symptomatic respiratory infection between December 2011 and May 2013. A subset of samples was tested for rhinovirus viral load by real-time polymerase chain reaction. Clinical data were collected by chart reviews. Multivariate logistic regression was used to evaluate the relationship between viral load and coinfection and the risk for LRTI. Results. Rhinovirus was the most frequent respiratory virus detected in children younger than 3 years. Of 445 patients with rhinovirus infection, 262 (58.9%) had LRTIs, 231 (51.9%) required hospital admission and 52 (22.5%) were hospitalized for 3 days or longer. Children with no comorbidities accounted for 142 (54%) of 262 rhinovirus LRTIs. Higher viral load was significantly associated with LRTI among illness episodes with rhinovirus alone (OR, 2.11; 95% confidence interval [CI], 1.24-3.58). Coinfection increased the risk of LRTI (OR, 1.83; 95% CI, 1.01-3.32). Conclusions. Rhinovirus was the most common pathogen detected among symptomatic young children in a pediatric ED who had respiratory viral testing performed, with the majority requiring hospitalization. Higher rhinovirus viral load and coinfection increased disease severity. Virologic data may assist clinical decision making for children with rhinovirus infections in the pediatric ED.
We managed recently a boy with acute parvovirus infection. A 14-yearold boy with hereditary spher... more We managed recently a boy with acute parvovirus infection. A 14-yearold boy with hereditary spherocytosis was brought to the hospital in shock. He had a 1-week history of fever, watery diarrhea and vomiting. On arrival, he was jaundiced and lethargic. Temperature was 38.1°C, heart rate 160/min, respiratory rate 28/min, blood pressure 90/40 mm Hg and O 2 saturation 94%. Splenomegaly unchanged from previous was present. Rash was absent, and he was mildly dehydrated.
N-(2-Hydroxypropyl) methacrylamide copolymer-5-fluorouracil (PHPMA-FU) conjugates were synthesize... more N-(2-Hydroxypropyl) methacrylamide copolymer-5-fluorouracil (PHPMA-FU) conjugates were synthesized by a novel and simplified synthetic route, and characterized by UV, FTIR and HPLC analyses. The conjugated content of 5-fluorouracil (5-FU) was 3.41±0.07wt%. The stabilities of PHPMA-FU conjugates under different conditions were studied. The results showed that HPMA copolymer was a potential carrier for tumor-targeting delivery of 5-FU.
We evaluated the Meridian IC-STAT direct fecal and broth culture antigen detection methods with s... more We evaluated the Meridian IC-STAT direct fecal and broth culture antigen detection methods with samples from children infected with Escherichia coli O157:H7 and correlated the antigen detection results with the culture results. Stools of 16 children who had recently had stool cultures positive for this pathogen (population A) and 102 children with diarrhea of unknown cause (population B) were tested with the IC-STAT device (direct testing). Fecal broth cultures were also tested with this device (broth testing). The results were correlated to a standard of the combined yield from direct culture of stools on sorbitol-MacConkey (SMAC) agar and culture of broth on SMAC agar. Eleven (69%) of the population A stool specimens yielded E. coli O157:H7 when plated directly on SMAC agar. Two more specimens yielded this pathogen when the broth culture was similarly plated. Of these 13 stool specimens, 8 and 13 were positive by direct and broth testing (respective sensitivities, 62 and 100%). Co...
The objective of this study is to describe the epidemiology of intestinal carriage with extended-... more The objective of this study is to describe the epidemiology of intestinal carriage with extended-spectrum-cephalosporin-resistant Enterobacteriaceae in children with index infections with these organisms. Patients with resistant Escherichia coli or Klebsiella bacteria isolated from the urine or a normally sterile site between January 2006 and December 2010 were included in this study. Available infection and stool isolates underwent phenotypic and molecular characterization. Clinical data relevant to the infections were collected and analyzed. Overall, 105 patients were identified with 106 extended-spectrum-cephalosporin-resistant E. coli (n = 92) or Klebsiella (n = 14) strains isolated from urine or a sterile site. Among the 27 patients who also had stool screening for resistant Enterobacteriaceae, 17 (63%) had intestinal carriage lasting a median of 199 days (range, 62 to 1,576). There were no significant differences in demographic, clinical, and microbiological variables between ...
To conduct a prospective cohort study to determine the frequency and characteristics of Shiga tox... more To conduct a prospective cohort study to determine the frequency and characteristics of Shiga toxin (Stx)-producing Escherichia coli (STEC) infections in children with diarrhea attending an emergency department and a private clinic in Seattle, Washington.
Annals of clinical microbiology and antimicrobials, Jan 15, 2004
Resistance to beta-lactam antibiotics in enteric Gram-negative bacilli may be difficult to detect... more Resistance to beta-lactam antibiotics in enteric Gram-negative bacilli may be difficult to detect using standard methods of either Kirby-Bauer disc diffusion (KBDD) or broth dilution for minimal inhibitory concentration (MIC). This difficulty is due to genetic differences in resistance determinants, differences in levels of gene expression, and variation in spectra of enzymatic activity against the substrate beta-lactams used for susceptibility testing. We have examined 95 clinical isolates reportedly susceptible to ceftazidime and ceftriaxone, as originally determined by either KBDD or MIC methods. The organisms studied here were isolated in 2002 from two pediatric hospital centers (Seattle, USA and Shanghai, China). They belong to the inducible beta-lactamase producing Gram-negative bacilli, such as Enterobacter spp., Citrobacter spp., Serratia spp., Morganella spp., Providencia spp., and Proteus vulgaris. A Kirby-Bauer disc approximation (KBDA) method identified inducible phenoty...
Background. A recent increase in Bordetella pertussis without the pertactin protein, an acellular... more Background. A recent increase in Bordetella pertussis without the pertactin protein, an acellular vaccine immunogen, has been reported in the United States. Determining whether pertactin-deficient (PRN -) B. pertussis is evading vaccine-induced immunity or altering the severity of illness is needed.
European Journal of Pharmaceutics and Biopharmaceutics, 2008
5-Fluorouracil (5-FU) is an antimetabolite with a broad-spectrum activity against solid tumors. H... more 5-Fluorouracil (5-FU) is an antimetabolite with a broad-spectrum activity against solid tumors. However, its very short half-life in plasma circulation greatly limited the in vivo antitumor efficacy and clinical application. The current work aimed to solve this problem as well as to increase 5-FU biodistribution to tumor by covalently conjugating 5-FU to a biocompatible, non-toxic and non-immunogenic drug carrier –N-(2-hydroxypropyl)
Crohn&amp... more Crohn's disease (CD) is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Fecal microbial transplant (FMT) is a potential therapeutic option for individuals with CD based on the hypothesis that changing the fecal dysbiosis could promote less intestinal inflammation. Nine patients, aged 12 to 19 years, with mild-to-moderate symptoms defined by Pediatric Crohn's Disease Activity Index (PCDAI of 10-29) were enrolled into a prospective open-label study of FMT in CD (FDA IND 14942). Patients received FMT by nasogastric tube with follow-up evaluations at 2, 6, and 12 weeks. PCDAI, C-reactive protein, and fecal calprotectin were evaluated at each study visit. All reported adverse events were graded as mild except for 1 individual who reported moderate abdominal pain after FMT. All adverse events were self-limiting. Metagenomic evaluation of stool microbiome indicated evidence of FMT engraftment in 7 of 9 patients. The mean PCDAI score improved with patients having a baseline of 19.7 ± 7.2, with improvement at 2 weeks to 6.4 ± 6.6 and at 6 weeks to 8.6 ± 4.9. Based on PCDAI, 7 of 9 patients were in remission at 2 weeks and 5 of 9 patients who did not receive additional medical therapy were in remission at 6 and 12 weeks. No or modest improvement was seen in patients who did not engraft or whose microbiome was most similar to their donor. This is the first study to demonstrate that FMT for CD may be a possible therapeutic option for CD. Further prospective studies are required to fully assess the safety and efficacy of the FMT in patients with CD.
Yakugaku Zasshi-journal of The Pharmaceutical Society of Japan, 2010
This paper reports both the optimization of aconitine entrapment and its release from biodegradab... more This paper reports both the optimization of aconitine entrapment and its release from biodegradable poly(d,l-lactide-coglycolide) (PLGA) nanoparticles prepared using the O/W single-emulsion/solvent-evaporation technique. The in‰uence of several parameters, such as the initial aconitine mass, aqueous-phase pH, volume ratio of aqueous/organic phase (W/O), PLGA concentration in the organic phase, etc., on aconitine encapsulation were investigated. The optimized nanoparticles had an entrapment e‹ciency of 88.40±3.02％ with drug loading capacity of 9.42±2.93％. Crystallization growth, which played a crucial role in hindering the incorporation of aconitine into the polymer carrier, was proposed. DiŠerential scanning calorimetry and X-ray powder diŠraction demonstrated that aconitine existed in an amorphous state or as a solid solution in the polymeric matrix. The in vitro release proˆles exhibited a sustained release of aconitine from nanoparticles and a pH-dependent character in phosphate-buŠered saline with diŠerent pH values. Moreover, aconitine-loaded PLGA nanoparticles could lead to improvement in the stability of aconitine. This work demonstrated the feasibility of encapsulating aconitine into PLGA nanoparticles using the O/W single-emulsion/solvent-evaporation technique.
International journal of pharmaceutics, Jan 12, 2008
In this study, the effects of alginate modification on absorption properties of FITC-BSA loaded T... more In this study, the effects of alginate modification on absorption properties of FITC-BSA loaded TMC nanoparticles were investigated on an in vitro model of GI epithelium (Caco-2 cells). The feasibility of applying TMC nanoparticles loaded with a model vaccine urease in oral vaccination was also studied. Alginate modified TMC nanoparticles showed higher FITC-BSA permeate efficiency than non-modified TMC nanoparticles. However, alginate modification barely had any effect on TMC nanoparticles' property of decreasing TEER or enhancing drug paracellular transport. Mice s.c. immunized with urease loaded TMC nanoparticles showed highest systematic immune response (IgG levels) but the lowest mucosal response (secretory IgA levels). In the contrast, mice i.g. immunized with urease loaded TMC nanoparticles showed much higher antibody titers of both IgG and secretory IgA than those with urease solution or urease co-administrated with TMC solution. These results indicated that TMC nanoparti...
Although pertussis disease is vaccine preventable, Washington State experienced a substantial ris... more Although pertussis disease is vaccine preventable, Washington State experienced a substantial rise in pertussis incidence beginning in 2011. By June 2012, the reported cases reached 2,520 (37.5 cases per 100,000 residents), a 1,300% increase compared with the same period in 2011. We assessed the molecular epidemiology of this statewide epidemic using 240 isolates collected from case patients reported from 19 of 39 Washington counties during 2012 to 2013. The typing methods included pulsed-field gel electrophoresis (PFGE), multilocus variable number tandem repeat analysis (MLVA), multilocus sequence typing (MLST), and pertactin gene (prn) mutational analysis. Using the scheme PFGE-MLVA-MLST-prn mutations-Prn deficiency, the 240 isolates comprised 65 distinct typing profiles. Thirty-one PFGE types were found, with the most common types, CDC013 (n = 51), CDC237 (n = 44), and CDC002 (n = 42), accounting for 57% of them. Eleven MLVA types were observed, mainly comprising type 27 (n = 183...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Jan 15, 2015
A recent increase in Bordetella pertussis without the pertactin protein, an acellular vaccine imm... more A recent increase in Bordetella pertussis without the pertactin protein, an acellular vaccine immunogen, has been reported in the United States. Determining whether pertactin-deficient (PRN(-)) B. pertussis is evading vaccine-induced immunity or altering the severity of illness is needed. We retrospectively assessed for associations between pertactin production and both clinical presentation and vaccine history. Cases with isolates collected between May 2011 and February 2013 from 8 states were included. We calculated unadjusted and adjusted odds ratios (ORs) using multivariable logistic regression analysis. Among 753 isolates, 640 (85%) were PRN(-). The age distribution differed between cases caused by PRN(-) B. pertussis and cases caused by B. pertussis producing pertactin (PRN(+)) (P = .01). The proportion reporting individual pertussis symptoms was similar between the 2 groups, except a higher proportion of PRN(+) case-patients reported apnea (P = .005). Twenty-two case-patients...
Emerging antibiotic resistance threatens human health. Gut microbes are an epidemiologically impo... more Emerging antibiotic resistance threatens human health. Gut microbes are an epidemiologically important reservoir of resistance genes (resistome), yet prior studies indicate that the true diversity of gut-associated resistomes has been underestimated. To deeply characterize the pediatric gut-associated resistome, we created metagenomic recombinant libraries in an Escherichia coli host using fecal DNA from 22 healthy infants and children (most without recent antibiotic exposure), and performed functional selections for resistance to 18 antibiotics from eight drug classes. Resistanceconferring DNA fragments were sequenced (Illumina HiSeq 2000), and reads assembled and annotated with the PARFuMS computational pipeline. Resistance to 14 of the 18 antibiotics was found in stools of infants and children. Recovered genes included chloramphenicol acetyltransferases, drug-resistant dihydrofolate reductases, rRNA methyltransferases, transcriptional regulators, multidrug efflux pumps, and every major class of beta-lactamase, aminoglycoside-modifying enzyme, and tetracycline resistance protein. Many resistance-conferring sequences were mobilizable; some had low identity to any known organism, emphasizing cryptic organisms as potentially important resistance reservoirs. We functionally confirmed three novel resistance genes, including a 16S rRNA methylase conferring aminoglycoside resistance, and two tetracyclineresistance proteins nearly identical to a bifidobacterial MFS transporter (B. longum s. longum JDM301). We provide the first report to our knowledge of resistance to folate-synthesis inhibitors conferred by a predicted Nudix hydrolase (part of the folate synthesis pathway). This functional metagenomic survey of gut-associated resistomes, the largest of its kind to date, demonstrates that fecal resistomes of healthy children are far more diverse than previously suspected, that clinically relevant resistance genes are present even without recent selective antibiotic pressure in the human host, and that cryptic gut microbes are an important resistance reservoir. The observed transferability of gut-associated resistance genes to a gram-negative (E. coli) host also suggests that the potential for gut-associated resistomes to threaten human health by mediating antibiotic resistance in pathogens warrants further investigation.
We managed recently a boy with acute parvovirus infection. A 14-yearold boy with hereditary spher... more We managed recently a boy with acute parvovirus infection. A 14-yearold boy with hereditary spherocytosis was brought to the hospital in shock. He had a 1-week history of fever, watery diarrhea and vomiting. On arrival, he was jaundiced and lethargic. Temperature was 38.1°C, heart rate 160/min, respiratory rate 28/min, blood pressure 90/40 mm Hg and O 2 saturation 94%. Splenomegaly unchanged from previous was present. Rash was absent, and he was mildly dehydrated.
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